The Morphology Core Facility will provide the Program Project with standardized morphological and immunohistochemical analyses of tissues obtained from tolerized hosts in the presence or absence of virus infection. Project #1 will use Core services for studies of the basic safety and durability of tolerance in mice given allografts and infected with various viral pathogens. Project #2 will use the Core for studies of the host immune response to allogeneic grafts in tolerant normal mice infected with viral pathogens, using allospecific T cell receptor transgenic model systems. Project #3 will use the Core for studies of chimerism and islet grafts in autoimmune, spontaneously diabetic NOD mice, treated by a new method to induce tolerance, in the presence and absence of viral infection. Each Project will by design require a large number of high- quality histological analyses for evaluation of graft rejection, graft survival, and, in Project 3, graft versus host disease (GVHD). The Core will be directed by a board-certified pathologist with extensive experience in the interpretation of clinical pathological specimens. his participation is designed to provide all projects with a consistent, high standard of interpretation of critical morphological data. The Core will also provide technicians who are well trained in both histology techniques and immunocytochemical assays. Examples of the data generated by members of the proposed Core will be found in the Preliminary Results Sections of the individual Projects, the Appendix to this Proposal, and in several of the Program's appended submitted manuscripts. The centralization of the morphologic studies in a Core directed by a pathologist with experience in supervising central service facilities is designed to facilitate collaborative research while obviating the need for each project to develop key techniques individually. In addition to conventional histology, tissue freezing, sectioning and fixing , the Core will provide immunohistochemistry for localization of hormone positive cells, heat induced epitope antigen retrieval, immunoperoxidase procedures for the identification of cell phenotype or cytokines, in situ hybridization, quality control procedures, and developmental assays.